Closing Kok's cycle of nature's water oxidation catalysis.

The MnCaO cluster in photosystem II catalyzes water splitting through the S state cycle (i = 0-4). Molecular O is formed and the natural catalyst is reset during the final S → (S) → S transition. Only recently experimental breakthroughs have emerged for this transition but without explicit information on the S-state reconstitution, thus the progression after O release remains elusive. In this report, our molecular dynamics simulations combined with density functional calculations suggest a likely missing link for closing the cycle, i.e., restoring the first catalytic state. Specifically, the formation of closed-cubane intermediates with all hexa-coordinate Mn is observed, which would undergo proton release, water dissociation, and ligand transfer to produce the open-cubane structure of the S state. Thereby, we theoretically identify the previously unknown structural isomerism in the S state that acts as the origin of the proposed structural flexibility prevailing in the cycle, which may be functionally important for nature's water oxidation catalysis.